Hepatitis B virus reactivation is an important medical issue in cancer patients who undergo systemic chemotherapy. Up to half of CHB carriers receiving chemotherapy develop hepatitis and among these cases a notable proportion are associated with HBV reactivation. However, the molecular mechanism(s) through which various chemotherapeutic agents induce HBV reactivation is not yet fully understood. In this study, we investigated the role of the cell cycle regulator p21 (Waf1/Cip1) in the modulation of HBV replication when a common chemotherapeutic agent, doxorubicin, is present. We showed that p21 expression was increased by doxorubicin treatment. This elevation in p21 expression enhanced the expression of CCAAT/enhancer-binding protein α (C/EBPα); such an increase is likely to promote the binding of C/EBPα to the HBV promoter, which will contribute to the activation of HBV replication. Our current study thus reveals the mechanism underlying doxorubicin modulation of HBV replication and provides an increased understanding of HBV reactivation in CHB patients who are receiving systemic chemotherapy.
Bioassay-guided fractionation of a MeOH extract of tubers of Coleus tuberosus afforded the active anti-tumor-promoting compounds identified as the triterpenoid 2alpha,3beta-dihydroxyolean-12-en-28-oic acid (maslinic acid; CT2) and a phytosterol mixture (CT1). CT1 consists of stigmasterol (32%), beta-sitosterol (40.3%), and campesterol (27.7%) as determined by capillary gas chromatography. CT1 and CT2 showed very strong anti-tumor-promoting activities at IC(50) 0.7 microg/ml and 0.1 microg/ml, respectively, in a convenient, short-term in vitro assay, i.e., the inhibition of Epstein-Barr virus (EBV) activation induced by phorbol 12-myristate 13-acetate (PMA) and sodium butyrate. We report for the first time the anti-tumor-promoting activity of 2alpha,3beta-dihydroxyolean-12-en-28-oic acid and show that a mixture of stigmasterol, beta-sitosterol, and campesterol is more potent than the individual components in inhibiting tumor-promoting activity.